This proposal is directed toward an understanding of the cellular and molecular mechanisms that control transport of IgG across the endothelial layer of the human placenta. Transport of mother's protective antibodies to the developing individual is vital to survival and is basic to maternal-fetal biology. Understanding this process is important for the health and well being of the fetus and newborn and will also have impact on a variety of disease states that devolve from IgG transport to the fetus. Additionally, understanding the IgG transport mechanism offers the potential for manipulation of the process for therapeutic purposes. Our basic hypothesis holds that IgG transport across the endothelium is an active process controlled by one of the known receptors for IgG, namely Fc-gamma-RIIb, and the specialized plasma membrane microdomains known as caveolae. The precise cellular and molecular details of this process are unknown. The experiments laid out in this proposal are designed to test our hypothesis and uncover the cellular and molecular mechanisms that permit transport of protective antibodies from mother to fetus. The specific aims of this proposal are to determine: (l) the potential for Fc-gammaRIIb to act as an IgG transporter and (2) the role that caveolae play in IgG transport. Our approaches to testing the predictions of this hypothesis incorporate methods of cell biology, immunology, biochemistry, ultrastructural analysis, and molecular biology.